Lurasidone hydrochloride, which has the chemical name ((3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)-piperazin-1-yl]methyl}cyclohexyl)-methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione hydrochloride, and is represented by formula 1

is an atypical antipsychotic used in the treatment of schizophrenia and bipolar disorders.
Lurasidone and a process for its preparation are disclosed in U.S. Pat. No. 5,532,372, wherein a compound of formula 2

and a quaternary ammonium salt of formula 3

are reacted by refluxing a mixture thereof in xylene in the presence of dibenzo-18-crown-6-ether and potassium carbonate. The free base obtained is then reacted with gaseous hydrochloric acid to form the hydrochloride.
This process has many drawbacks; for example, dibenzo-18-crown-6 is a highly toxic, expensive substance and is not suitable for drug manufacturing nor for industrial production. Moreover, the use of alkali metal carbonates such as potassium carbonate results in the formation of a by-product or series of by-products containing the carbonate moiety. Additionally, the reaction system is heterogeneous, so it is difficult to maintain stable reaction times on an industrial scale. Finally, the use of gaseous hydrochloric acid is hard to apply on an industrial scale because it has many drawbacks in terms of safety of operators, equipment and the environment.
A similar method for preparing lurasidone is disclosed in patent application US 2011/0263847. Said patent describes the synthesis of the compound of formula 3 as a first step, by reacting a compound of formula 4 with a compound of formula 5 in toluene with a solid inorganic base such as potassium carbonate

In the second step, a compound of formula 2 is then added to the quaternary ammonium salt 3 obtained in the same reaction vessel, and reacted with a solid organic base to obtain lurasidone.
This process also suffers from the same drawbacks as the previous one, i.e. the formation of a carbonate impurity, which is described in the patent application as a “by-product (R)”, and the reaction medium is still heterogeneous. Moreover, the desired product is obtained in a mixture with inorganic salts, making it necessary to perform solvent extractions and subsequent purifications to isolate lurasidone. This process is clearly difficult to scale up to an industrial scale.
Another method is disclosed in US patent application 2011/0263848. This document describes the same process as US 2011/0263847, but using a phosphate salt during the preparation of compound 3 (first step), while the second step, i.e. the lurasidone formation reaction, is still performed with potassium carbonate. This process still suffers from the same drawbacks as US 2011/0263847, i.e. a heterogeneous reaction system and formation of “by-product (R)”.
There is thus a need for an efficient process for the preparation of lurasidone hydrochloride which uses less toxic reagents, and can be applied on an industrial scale without the formation of impurities which are hard to remove.